Creatinine is a byproduct of normal skeletal muscle creatine metabolism and is freely filtered across the glomerulus into Bowman’s space. It is normally generated by the body at a fairly constant rate, and—to a first approximation—it is not appreciably reabsorbed, secreted, or metabolized by the cells of the nephron after its filtration. Accordingly the amount of creatinine excreted in urine per minute is fairly constant at steady state (i.e., when [creatinine] is constant) and equals the amount of creatinine filtered at the glomerulus each minute (
Fig. 33.13): cFor most substances cleared from plasma by the kidneys, only a portion is actually removed and excreted in a single pass through the kidneys.
Equation 33.7 where PCr = plasma concentration of creatinine UCr = urine concentration of creatinine V̇ = urine flow
Eq. 33.7 is solved for GFR:
Equation 33.8
This equation is the same form as that for clearance (see
Eq.
33.4 ). Thus measured creatinine clearance (CrCl) can be used clinically to determine GFR at steady state. Clearance has the dimensions of volume/time, and it represents an equivalent volume of plasma from which all of the substance has been removed and excreted into urine per unit time.
Creatinine is not the only substance that can be used to measure GFR; any substance that meets the following criteria can serve as an appropriate marker. The substance must: 1.
2.
be freely filtered across the glomerulus into Bowman’s space 3.
not be reabsorbed or secreted by the nephron 4.
not be metabolized or produced by the kidney 5.
Not all creatinine (or other substances used to measure GFR) that enters the kidney in renal arterial plasma is filtered at the glomerulus. Likewise not all plasma coming into the kidneys is filtered. Although nearly all plasma that enters the kidneys in the renal artery passes through the glomerulus, approximately 10% does not. The portion of filtered plasma is termed the filtration fraction and is determined as:
Equation 33.9
Under normal conditions the filtration fraction averages 0.15 to 0.20, which means that only 15% to 20% of the plasma that enters the glomerulus is actually filtered. The remaining 80% to 85% continues on through the glomerular capillaries and into the efferent arterioles and peritubular capillaries before finally returning to the systemic circulation via the renal vein.
The first step in the formation of urine is ultrafiltration of plasma by the glomerulus. In normal adults, GFR ranges from 90 to 140 mL/min in males and from 80 to 125 mL/ min in females. Thus in 24 hours as much as 180 L of plasma is filtered by the glomeruli. The plasma ultrafiltrate is devoid of cellular elements (i.e., red and white blood cells and
Creatinine clearance (CrCl) is used to estimate GFR in clinical practice. It is synthesized at a relatively constant rate, and the amount produced is proportional to the total muscle mass. However, creatinine is not a perfect substance for measuring GFR because it is secreted to a small extent by the organic cation secretory system in the proximal tubule (see ). The error introduced by this secretory component is approximately 10%. Thus the amount of creatinine excreted in urine exceeds the amount expected from filtration alone by 10%. However, the method used to measure the plasma creatinine concentration (PCr) overestimates the true value by 10%. Consequently the two errors cancel each other, and in most clinical situations, CrCl provides a reasonably accurate measure of GFR.